Design and Pharmacological Chaperone Effects of -(4'-Phenylbutyl)-DAB Derivatives Targeting the Lipophilic Pocket of Lysosomal Acid α-Glucosidase.

This study provides the first example of a strategy to design a practical ligand toward lysosomal acid α-glucosidase (GAA) focusing on -alkyl derivatives of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB). The optimized -4'-(-trifluoromethylphenyl)butyl-DAB () showed a value of 0.73 μM, which was 353-fold higher affinity than -butyl-DAB () without a terminal phenyl group.